Journal article
The BRCA2 c.68-7T > A variant is not pathogenic: A model for clinical calibration of spliceogenicity
M Colombo, I Lòpez-Perolio, HD Meeks, L Caleca, MT Parsons, H Li, G De Vecchi, E Tudini, C Foglia, P Mondini, S Manoukian, R Behar, EBG Garcia, A Meindl, M Montagna, D Niederacher, AY Schmidt, L Varesco, B Wappenschmidt, MK Bolla Show all
Human Mutation | WILEY-HINDAWI | Published : 2018
DOI: 10.1002/humu.23411
Abstract
Although the spliceogenic nature of the BRCA2 c.68-7T > A variant has been demonstrated, its association with cancer risk remains controversial. In this study, we accurately quantified by real-time PCR and digital PCR (dPCR), the BRCA2 isoforms retaining or missing exon 3. In addition, the combined odds ratio for causality of the variant was estimated using genetic and clinical data, and its associated cancer risk was estimated by case-control analysis in 83,636 individuals. Co-occurrence in trans with pathogenic BRCA2 variants was assessed in 5,382 families. Exon 3 exclusion rate was 4.5-fold higher in variant carriers (13%) than controls (3%), indicating an exclusion rate for the c.68-7T >..
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Grants
Awarded by National Breast Cancer Foundation
Funding Acknowledgements
the NHMRC Senior Research Fellowship Scheme; Spanish Instituto de Salud Carlos III funding, an initiative of the Spanish Ministry of Economy and Innovation partially supported by European Regional Development FEDER Funds; Associazione Italiana per la Ricerca sul Cancro, Grant/Award Number: No15547 to P.R.; the Cancer Council Queensland; NHMRC Project grant scheme